The coordinate genetic regulation of glycolysis by hypoxia will be studied in cell systems by measurements of glycolytic enzyme content, rates of biosynthesis and degradation; measurements of levels of specific mRNA for the various glycolytic enzymes and measurements of the rates of biosynthesis and degradation of the specific mRNAs. A variety of cell models will be used. The regulation of genetic expression in mitochondria by hypoxia will be studied in isolated cell systems and organs by measurements of mt enzyme activity and content, measurements of mt DNA and mt 16S ribosomal RNA. Alterations in collagen metabolism in fibroblasts at a genetic level by hyperoxia, hypoxia, Bleomycin and phagocytes will be studied in various fibroblast systems. The possibility of coordinate genetic regulation of collagen biosynthesis will be studied by investigating alterations in specific mRNA for the 6 post-translational enzymes. In addition, the proposal will be used as a training format for medical students, pre-doctoral PhD candidates, post-doctoral MD fellows and post-doctoral PhD fellows through separate funding.